This is a revised application for the Mentored Clinical Scientist Development Award (K08). My overall goal is to obtain sufficient experience and expertise in laboratory investigation to function as an independent researcher in the field of alcohol and traumatic brain injury (TBI). I plan to conduct research that will eventually lead to a reduction in morbidity and mortality from alcohol-related trauma. My preceptor for this proposal is A. Lorris Betz, MD, PhD. My career development requirements include basic science training in laboratory research design, methodology and techniques. I will meet my basic science training needs by working directly with experienced investigators in the fields of alcohol biochemistry and neurochemistry, brain injury, physiology, and pharmacology. This will include direct supervision of my experiments, observation in other investigators' labs, educational courses, and local and national scientific conferences. I will also complete courses in research design and methods, data analysis and management, biostatistics, grant-writing, and research ethics. In addition, I will learn more about clinical work in alcohol and injury by consulting on a regular basis with experienced investigators as they conduct funded clinical studies. I have developed a five year research plan with the goal of defining the mechanisms behind ethanol-induced respiratory depression following TBI. We will utilize a porcine fluid percussion TBI model that I have developed over the past several years. The plan includes laboratory investigations in 2 phases. The first phase deals with the interrelationships between respiratory depression, cerebral perfusion, brain acidosis, and ethanol intoxication. The second phase explores receptor interactions in the brain, including ethanol effects on opiate, GABA, and NMDA receptors following TBI. The proposed experiments will be the first to comprehensively monitor ventilation, cerebral perfusion pressure, cerebral blood flow, and metabolic and cardiovascular parameters in an alcohol/injury model. We will also perform assays on brain tissue to define neurochemical and receptor activity for each phase, including measurement of brain lactate, GABA, glutamate and endorphin levels. I will work closely with Dr. Betz and the consultants in my laboratory and in their laboratories to learn and perfect techniques to assess the physiologic and neurochemical basis for ethanol- induced respiratory depression following TBI. With the help of K08 Award support I intend, after 5 years, to be able to function as an independent investigator, with the requisite skills and knowledge to pursue a career in alcohol research.